Field of the Invention
The present invention relates to the field of pharmaceutical chemistry, and in particular, to coumarin-gossypol derivatives with antitumor activities of and a method of preparing the same.
Discussion of the Related Art
Gossypol is a polyphenolic bis-naphthalene aldehyde compound, and a natural yellow pigment found in small cell glands between cotton cells. Its structure was determined in 1938. Gossypol is recognized as an effective male contraceptive agent, but at the same time it also has large toxicity. The two aldehydes in its molecule not only play a role in tautomerization but also increase its chemical activities. They may contribute to its toxicity. As a new natural product with potential, in the early 1960s, the antitumor activity of gossypol was confirmed. Studies have shown that the anti-tumor mechanism of gossypol relates to its ability to inhibit the activation of topoisomerase II and the stability of topoisomerase-DNA complex formation, affecting cell functions. Gossypol also activates the expression of TGF-β1 in prostate cancer cell line PC3, and inhibits cell DNA synthesis and terminates cells in G0/G1 phase. In view of its antitumor activities, in recent years, the study of anti-tumor mechanism of gossypol has become active.
Coumarin derivatives are a class of oral anticoagulant drugs. A common structure is 4-hydroxycoumarin. The core structure of coumarin derivatives is 1-benzopyran-2-one, which can be substituted with hxdroxyl, alkoxy, phenyl, isopentenyl, and other groups. Coumarin derivatives may have anti-HIV, anti-cancer, antihypertensive, antiarrhythmic, anti-osteoporosis, analgesic, asthma and antibacterial and other biological activities. They are also widely used natural spices.
Gossypol is known as male contraceptives and has been widely concerned with its excellent anti-tumor properties. Coumarin is a kind of natural organic matter which is very important in nature. It is simple in structure and high in biological activity. Therefore, the present invention utilizes the aldehyde group of gossypol and the active site of the coumarin in the coumarin structure to synthesize a kind of gossypol derivative with coumarin structure to achieve better anti-tumor activity.
Gossypol is known as male contraceptives and having some anti-tumor activities. As a nature product, coumarin has a simple structure and bioactivities.
The present invention utilizes the aldehyde group of gossypol and the active site in the coumarin structure to synthesize coumarin-gossypol derivatives to achieve better anti-tumor activities and lower toxicities.